P775: LONG-TERM EFFICACY AND SAFETY OF POZELIMAB MONOTHERAPY IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
Authors: Jun-Ho Jang, Raymond Wong, Jonathan Weyne, Umesh Chaudhari, Jutta Miller, Quang P. Nguyen, Morag Griffin
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease characterized by chronic intravascular hemolysis and increased risk of thrombosis. Pozelimab is an investigational monoclonal antibody inhibitor of complement component C5. Aims: To present final results from a phase 2, open-label, single-arm study (NCT03946748), and subsequent open-label extension (OLE; NCT04162470), evaluating the long-term efficacy and safety of pozelimab monotherapy in patients with PNH. Methods: The 26-week study enrolled 24 patients. Patients received a single intravenous loading dose of pozelimab 30 mg/kg, followed by a weekly subcutaneous (SC) dose of 800 mg through to Week 26. All patients who completed the phase 2 study were eligible to enroll in the OLE, and were maintained on weekly SC pozelimab 800 mg up to Week 104. Results: All 24 patients completed the phase 2 study and enrolled into the OLE; 87.5% were Asian and 54.2% were male. In phase 2, pozelimab led to rapid and sustained reduction in lactate dehydrogenase (LDH) through Week 26. At every scheduled time point between Weeks 4 through 26 inclusive, 18/24 (75.0%) patients achieved adequate control of their intravascular hemolysis (defined as LDH ≤1.5 x upper limit of normal, 95% confidence interval [CI]: 57.7–92.3%). During the OLE, 23 (95.8%) and 15 (62.5%) patients completed treatment through to Week 26 and Week 78, respectively. Control of intravascular hemolysis was achieved by 22/23 (95.7%) patients at all time points through to Week 26 of the OLE (95% CI: 87.3–100.0%); for Week 78, the results were 15/16 (93.8%; 95% CI: 81.9–100.0%). At each study visit, 83–100% of patients achieved adequate control of hemolysis for both phase 2 and OLE trials (Figure 1). In phase 2, 21/24 (87.5%; 95% CI: 74.3–100.0%) patients achieved transfusion avoidance (no post-baseline transfusion of red blood cells). During the OLE, 22/23 (95.7%) patients achieved transfusion avoidance through the initial 26 weeks, and 15/16 (93.8%) through to Week 78. No patients experienced a breakthrough hemolysis event in either trial. Importantly, one patient with a C5 variant known to be resistant to blockade by eculizumab/ravulizumab had adequate control of intravascular hemolysis and achieved transfusion avoidance. All patients showed a rapid decrease in total complement hemolytic activity to near zero, which was maintained up to Week 104. In phase 2, 21 (87.5%) patients experienced a total of 72 treatment-emergent adverse events (TEAEs). Two (8.3%) patients experienced severe TEAEs; 10 (41.7%) patients experienced TEAEs considered related to pozelimab treatment. During the OLE, 15 (62.5%) patients experienced a total of 41 TEAEs; two (8.3%) patients experienced serious TEAEs; two (8.3%) patients experienced severe TEAEs; and two (8.3%) patients experienced TEAEs considered related to pozelimab treatment. No deaths or discontinuations due to TEAEs occurred during the OLE. Summary/Conclusion: Patients treated with pozelimab (up to 130 weeks) experienced improvement in control of their intravascular hemolysis, saw no breakthrough hemolysis, and were able to achieve transfusion avoidance. Pozelimab was also generally well tolerated. Pozelimab may be a potentially effective long-term treatment for patients with PNH.Keywords: Complement, Clinical trial, Hemolysis, PNH